Connective tissue, Ehlers-Danlos syndrome(s), and head and cervical pain

Am J Med Genet C Semin Med Genet. 2015 Mar;169C(1):84-96. doi: 10.1002/ajmg.c.31426. Epub 2015 Feb 5.


Ehlers-Danlos syndrome (EDS) is an umbrella term for a growing group of hereditary disorders of the connective tissue mainly manifesting with generalized joint hypermobility, skin hyperextensibility, and vascular and internal organ fragility. In contrast with other well known heritable connective tissue disorders with severe cardiovascular involvement (e.g., Marfan syndrome), most EDS patients share a nearly normal life span, but are severely limited by disabling features, such as pain, fatigue and headache. In this work, pertinent literature is reviewed with focus on prevalence, features and possible pathogenic mechanisms of headache in EDSs. Gathered data are fragmented and generally have a low level of evidence. Headache is reported in no less than 1/3 of the patients. Migraine results the most common type in the hypermobility type of EDS. Other possibly related headache disorders include tension-type headache, new daily persistent headache, headache attributed to spontaneous cerebrospinal fluid leakage, headache secondary to Chiari malformation, cervicogenic headache and neck-tongue syndrome, whose association still lacks of reliable prevalence studies. The underlying pathogenesis seems complex and variably associated with cardiovascular dysautonomia, cervical spine and temporomandibular joint instability/dysfunction, meningeal fragility, poor sleep quality, pain-killer drugs overuse and central sensitization. Particular attention is posed on a presumed subclinical cervical spine dysfunction. Standard treatment is always symptomatic and usually unsuccessful. Assessment and management procedures are discussed in order to put some basis for ameliorating the actual patients' needs and nurturing future research.

Keywords: POTS; cervical spine; connective tissue; ligamentous laxity; meninges; occipitoatlantoaxial; temporomandibular.

Publication types

  • Review

MeSH terms

  • Connective Tissue / pathology
  • Disease Management
  • Ehlers-Danlos Syndrome / complications
  • Ehlers-Danlos Syndrome / physiopathology*
  • Fatigue / etiology
  • Fatigue / pathology
  • Headache / etiology
  • Headache / physiopathology*
  • Humans
  • Neck Pain / etiology
  • Neck Pain / physiopathology*